A Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effect of Randomized, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060380 in Healthy and Elevated LDL-C Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- AE
研究概览
简要总结
Study to Evaluate Safety, Tolerability and Pharmacokinetics of CS060380 in Healthy and Elevated LDL-C Subjects.
详细描述
A Phase I study Evaluating the Safety, Tolerability, Pharmacokinetics and Food Effects of Randomised, Double-Blind, Placebo-Controlled Single and Multiple Dose Escalations of CS060380 in Healthy and Elevated LDL-C Subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Sign and date the ICF.
- •Signing ICF age≥18 years≤55 years, male or female.
- •Weight: Male≥50kg, female≥45kg BMI: 18~28kg/m².
- •Female or male subjects must be eligible for contraception during the study.
- •Normal renal function.
- •Good general health.
- •No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.
- •Understand and comply with study procedures and limitations.
- •Sign and date the ICF.
- •Signing ICF age≥18 years≤65 years, male or female.
- •Weight: Male≥50kg, female≥45kg BMI: 18~35kg/m², including at least 25% of overweight subjects ( BMI : 25~30 kg/m² ), and at least 25% of obese subjects (BMI≥ 30 kg/m² ).
- •Screening period, fasting LDL-C > 110 mg/dL (2.85 mmol/L).
- •Female or male subjects must be eligible for contraception during the study.
- •Normal renal function (calculate glomerular filtration rate using CKD-EPI equation≥ 80mL/min/1.73m² ).
- •Good general health.
- •No significant medical history, in good general health as assessed by the study during the Screening Period and no more than 28 days from the first dose.
排除标准
- •Special dietary requirements, not following a uniform diet.
- •Pregnant or nursing females or females who have pregnancy plans during the trial or within 3 months after the trial.
- •History of febrile illness or active infection within 7 days prior to first dose.
- •Positive urine drug screening results.
- •History of drug/substance abuse experiments within the past 5 years prior to the start, The baseline drug screening result is positive.
- •History of previous corrected QT interval (QTc) prolongation:
- •Screening periods QTcF ≥ 450 ms.
- •Family history of hypocalcaemia or long QT interval syndrome.
- •Use of drugs causing QT/QTc prolongation.
- •Investigator judgement of clinically significant abnormal ECG results.
- •Abnormal liver function: AST, ALT, ALP, GGT and TBIL>ULN.
- •Smoking or use of nicotine products within 3 months prior to screening and during the study period.
- •Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
- •Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody tests.
- •Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
- •Blood loss within 40 days prior to administration 50~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
- •Drinking alcohol 48 hours before screening or during CRU period.
- •Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
- •History of thyroid disease or clinically significant thyroid test abnormalities.
- •Allergy to thyroid medication.
- •Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
- •According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
- •Allergy to the investigational drug or any component of the investigational drug, allergy history and constitution.
- •Diseases or conditions with clinical significance that researchers believe may pose a risk to the safety of subjects or interfere with the conduct, progress, or completion of the study.
- •Abnormal thyroid function test during screening.
- •Screening or baseline cardiac troponin>ULN.
- •Special dietary requirements that cannot follow a unified diet.
- •Pregnant or lactating women who have a pregnancy plan during or within 3 months after the trial, female subjects tested positive for pregnancy during screening or baseline period.
- •Individuals with a history of febrile diseases or active infections within 7 days prior to the first administration of medication.
- •Positive urine drug screening results during screening or baseline period.
- •History of drug/drug abuse within 5 years prior to the start of the trial, or positive drug screening results during screening or baseline period.
- •Subjects who are receiving lipid-lowering treatment or have LDL-C>190 mg/dL and have a family history of coronary heart disease, arrhythmia, unexplained syncope, or cardiac arrest.
- •History of QTc extension in the past:
- •Screening period QTcF ≥ 450 ms.
- •Family history of hypocalcemia or long QT interval syndrome.
- •Using drugs that cause QT/QTc prolongation.
- •Abnormal results of ECG with clinical significance determined by researchers.
- •Abnormal liver function: AST, ALT, ALP, GGT and TBIL>ULN.
- •Screening for smoking or using nicotine products within the first 3 months and during the study period.
- •Use of other investigational drugs 40 days prior to enrolment or within at least 5 half-lives of drug use.
- •Positive screening results for infectious diseases during the screening period, include HIV, HBsAg, HBcAb, HCV antibody Tests.
- •Any abnormal results of laboratory tests judged by the investigator to be clinically significant during the screening period.
- •Blood loss within 40 days prior to administration 50~500 mL, or loss of more than 500 mL of blood within 56 days prior to administration.
- •Men and women who consumed more than 1 unit per day prior to screening, [1 unit = 150 ml of wine, 360 ml of beer or 45 ml of 40% alcohol], drinking alcohol 48 hours before administration and during CRU.
- •Prescription and over-the-counter use within 14 days or at least 5 half-lives prior to the baseline period, or use of any drug or other substance that may affect CYP3A activity within 14 days or at least 5 half-lives before taking this study drug.
- •History of thyroid disease or clinically significant thyroid test abnormalities.
- •Allergy to thyroid medication.
- •Presence of any disease that may interfere with the absorption, distribution, metabolism or excretion of drugs, Including bile salt metabolism in the colon, such as gastrectomy, inflammatory bowel disease, etc.
- •According to the researcher's judgment, there are clinically significant diseases found, including but not limited to (gastrointestinal, kidney, liver, nervous, blood, endocrine, tumor, lung, immune, mental or cardiovascular diseases), researchers believe that participating in the study poses risks to participants.
- •Allergy to the investigational drug or any component of the investigational drug, Allergy history and constitution.
- 另有 3 项未显示
研究组 & 干预措施
Cohort D1: 0.1 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort A1: 0.2 mg CS060380
Eight healthy subjects were randomly assigned to take 0.2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).
干预措施: CS060380 (Drug)
Cohort A2: 1 mg CS060380
Eight healthy subjects were randomly assigned to take 1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).
干预措施: CS060380 (Drug)
Cohort A3: 2 mg CS060380
Eight healthy subjects were randomly assigned to take 2 mg of CS060380 or placebo on day 1, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach). Followed by a 10 day washout period, subjects in fed state will receive the same single oral dose of CS060380 2mg or placebo on day 11.
干预措施: CS060380 (Drug)
Cohort A4: 5 mg CS060380
Eight healthy subjects were randomly assigned to take 5 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).
干预措施: CS060380 (Drug)
Cohort A5: 10 mg CS060380
Eight healthy subjects were randomly assigned to take 10 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo (About 240L of water on an empty stomach).
干预措施: CS060380 (Drug)
Cohort B1: 1 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 1 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort B2: 2 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort C1: 0.25 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.25 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort C2: 0.5 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.5 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort C3: 0.75 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.75 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort D2: 0.15 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.15 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
Cohort D3: 0.2 mg CS060380
Elevated LDL-C subjects were randomly assigned to take 0.2 mg of CS060380 or placebo, Six of the subjects were on study drug and two on placebo once daily for a consecutive 14 days.
干预措施: CS060380 (Drug)
结局指标
主要结局
AE
时间窗: Day1 to Day 28
occurrence rate of AEs
次要结局
- Single-Dose Pharmacokinetic (PK) Parameter (AUC0-∞)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (AUC0-last)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (Cmax)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (Tmax)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (T1/2)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (CL/F)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (Kel)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (MRT)(Day 1, day 2, day3, day4.)
- Single-Dose Pharmacokinetic (PK) Parameter (Vz/F)(Day 1, day 2, day3, day4.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_max)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_min)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (AUCtau)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (Tmax)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (T1/2)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (CL/F)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (DF)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (Ct_av)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)
- Multiple-Dose Pharmacokinetic (PK) Parameter (Rac)(Day 1, day 2, day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, day 15.)